A chimeric antigen receptor targeting bcma and its application

Abstract

The invention relates to a chimeric antigen acceptor of a target BCMA (B cell maturation antigen). The chimeric antigen acceptor comprises an extracellular identification region, a hinge region, a transmembrane region and an intracellular signal region, wherein the extracellular identification region has a BCMA resisting nanometer antibody sequence, and the BCMA resisting nanometer antibody sequence is a heavy-chain variable region sequence combining with BCMA and from alpacas. More specifically, the BCMA resisting nanometer antibody sequence is BCMA monoclonal antibody B1 or B65, the amino acid sequence of the B1 is as shown in SEQID NO.1, and the amino acid sequence of the B65 is as shown in SEQID NO.2. According to the chimeric antigen acceptor disclosed by the invention, compared witha traditional mouse-derived SCFV or humanized SCFV, the nanometer antibody from the alpacas is used, and has small molecule quantity and immunogenicity, the possibility that CAR-T cells prepared on the base of the nanometer antibody produce HAMA effects in vivo is smaller, the remaining time of the CAR-T cells in vivo can be longer, the CAR-T cells pass through BCMA protein on the surfaces of target tumor cells and activate signal channels at the downstream part of T cells, the capacity for killing tumor cells having BCMA target points is given to the T cells, and BCMA positive blood tumor canbe efficiently and specifically treated.

Description

technical field [0001] The invention relates to the technical field of cellular immunotherapy, in particular to a chimeric antigen receptor targeting BCMA and its application. Background technique [0002] B cell maturation antigen (BCMA) is an antigen expressed on plasma cells, plasmablasts and bone marrow plasma cells, but not on B cells or hematopoietic stem cells. The expression of BCMA is associated with many cancers, autoimmune diseases and infectious diseases. Cancers with increased BCMA expression include some blood cancers such as multiple myeloma, Hodgkin's and non-Hodgkin's lymphomas, various leukemias and glioblastoma, among others. This limited expression cell type makes BCMA a possible target for the treatment of hematological tumors to develop therapies such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and CAR-T. There are currently no drugs targeting BCMA on the market, but there are a few therapies targeting BCMA to treat mult...

AI Technical Summary

Problems solved by technology

There are currently no drugs targeting BCMA on the market, but there are a few therapies targeting BCMA to treat multiple myeloma through antibody-coupled drugs, CAR-T therapy, etc. The application in the field of tumors has achieved certain results. Data from European and American clinical trials show that the existing BCMA chimeric antigen receptor T (carT) technology has an objective cure rate (objective response, OBB) of about 50% in the treatment of multiple myeloma, but there are still The clinical shortcomings are as follows: the effective rate of treatment is lower than the typical CD19carT70-90% complete cure rate, and the effective rate needs to be improved

[0003] Nanobodies are currently known as the smallest unit that can bind to target antigens, with a molecular weight of only 15KD, which is one tenth of that of traditional antibodies; mouse antibodies, which are widely used in clinical practice, are more immunogenic and more likely to produce HAMA effects. That is, the human anti-mouse antibody effect, which will cause the mouse-derived monoclonal antibody to have the immunogenicity of foreign proteins to the human body, and has a short half-life in the human body. Repeated use can cause the production of human anti-mouse antibody (HAMA), thereby make its application limited

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